Publications by authors named "Robert J Thomas"

158 Publications

Obstructive sleep apnea phenotypes and cardiovascular risk: Is there a role for heart rate variability in risk stratification?

Sleep 2021 05;44(5)

Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1093/sleep/zsab037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120334PMC
May 2021

Sleep structure and electroencephalographic spectral power of middle-aged or older adults: Normative values by age and sex in the Korean population.

J Sleep Res 2021 May 5:e13358. Epub 2021 May 5.

Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Korea.

The fine structure of sleep electrocortical activity reflects health and disease. The current study provides normative data for sleep structure and electroencephalography (EEG) spectral power measures derived from overnight polysomnography (PSG) and examines the effect of age and sex among Korean middle-aged and older adults with or without obstructive sleep apnea (OSA). We analysed home PSG data from 1,153 adult participants of an ongoing population-based cohort study, the Korean Genome and Epidemiology Study. Sleep stages were visually scored and spectral power was measured on a single-channel EEG (C4-A1). We computed spectral power for five frequency ranges. The EEG power was reported in relative (%) and log-transformed absolute values (µV ). With ageing, the proportion of N1 sleep increased, whereas N3 decreased, which is more noticeable in men than in women. The amount of N3 was relatively low in this cohort. With ageing, relative delta power decreased and alpha and sigma power increased for the whole sleep period, which was more pronounced during REM sleep in non-OSA. For men compared with women, relative theta power was lower during REM and sigma and beta were higher during N1 sleep. The differences of relative powers by age and sex in OSA were comparable to those in non-OSA. In a community-based Korean population, we present normative data of sleep structure and spectral power for middle-aged or older adults of a non-Caucasian ethnicity. The values varied with age and sex and were not influenced by sleep apnea.
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http://dx.doi.org/10.1111/jsr.13358DOI Listing
May 2021

HIV Increases Sleep-based Brain Age Despite Antiretroviral Therapy.

Sleep 2021 Mar 30. Epub 2021 Mar 30.

Massachusetts General Hospital, Boston, MA, USA.

Study Objectives: Age-related comorbidities and immune activation raise concern for advanced brain aging in people living with HIV (PLWH). The brain age index (BAI) is a machine learning model that quantifies deviations in brain activity during sleep relative to healthy individuals of the same age. High BAI was previously found to be associated with neurological, psychiatric, cardiometabolic diseases, and reduced life expectancy among people without HIV. Here, we estimated the effect of HIV infection on BAI by comparing PLWH and HIV-controls.

Methods: Clinical data and sleep EEGs from 43 PLWH on antiretroviral therapy (HIV+) and 3,155 controls (HIV-) were collected from Massachusetts General Hospital. The effect of HIV infection on BAI, and on individual EEG features, was estimated using causal inference.

Results: The average effect of HIV on BAI was estimated to be +3.35 years (p < 0.01, 95% CI = [0.67, 5.92]) using doubly robust estimation. Compared to HIV- controls, HIV+ participants exhibited a reduction in delta band power during deep sleep and rapid eye movement sleep.

Conclusion: We provide causal evidence that HIV contributes to advanced brain aging reflected in sleep EEG. A better understanding is greatly needed of potential therapeutic targets to mitigate the effect of HIV on brain health, potentially including sleep disorders and cardiovascular disease.
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http://dx.doi.org/10.1093/sleep/zsab058DOI Listing
March 2021

Current trends in flow cytometry automated data analysis software.

Cytometry A 2021 Feb 19. Epub 2021 Feb 19.

Centre for Biological Engineering, Loughborough University, Loughborough, Leicestershire, United Kingdom.

Automated flow cytometry (FC) data analysis tools for cell population identification and characterization are increasingly being used in academic, biotechnology, pharmaceutical, and clinical laboratories. The development of these computational methods is designed to overcome reproducibility and process bottleneck issues in manual gating, however, the take-up of these tools remains (anecdotally) low. Here, we performed a comprehensive literature survey of state-of-the-art computational tools typically published by research, clinical, and biomanufacturing laboratories for automated FC data analysis and identified popular tools based on literature citation counts. Dimensionality reduction methods ranked highly, such as generic t-distributed stochastic neighbor embedding (t-SNE) and its initial Matlab-based implementation for cytometry data viSNE. Software with graphical user interfaces also ranked highly, including PhenoGraph, SPADE1, FlowSOM, and Citrus, with unsupervised learning methods outnumbering supervised learning methods, and algorithm type popularity spread across K-Means, hierarchical, density-based, model-based, and other classes of clustering algorithms. Additionally, to illustrate the actual use typically within clinical spaces alongside frequent citations, a survey issued by UK NEQAS Leucocyte Immunophenotyping to identify software usage trends among clinical laboratories was completed. The survey revealed 53% of laboratories have not yet taken up automated cell population identification methods, though among those that have, Infinicyt software is the most frequently identified. Survey respondents considered data output quality to be the most important factor when using automated FC data analysis software, followed by software speed and level of technical support. This review found differences in software usage between biomedical institutions, with tools for discovery, data exploration, and visualization more popular in academia, whereas automated tools for specialized targeted analysis that apply supervised learning methods were more used in clinical settings.
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http://dx.doi.org/10.1002/cyto.a.24320DOI Listing
February 2021

Automated Apnea-Hypopnea Index from Oximetry and Spectral Analysis of Cardiopulmonary Coupling.

Ann Am Thorac Soc 2021 05;18(5):876-883

Division of Pulmonary and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

The increased prevalence of obstructive sleep apnea (OSA) coincides with a severe shortage of sleep physicians. There is a need for widescale home-sleep-testing devices with accurate automated scoring to accelerate access to treatment. To examine the accuracy of an automated apnea-index (AHI) derived from spectral analysis of cardiopulmonary coupling (CPC) extracted from electrocardiograms, combined with oximetry signals, in relation to polysomnograms (PSGs). Electrocardiograms and pulse-oximeter tracings on PSGs from APPLES (Apnea Positive Pressure Long-term Efficacy Study) were analyzed. Distinct CPC spectral bands were combined with the oxygen desaturation index to create a derived AHI (DAHI). Correlation statistics between the DAHI and the conventionally scored AHI, in which hypopneas required ≥50% airflow reduction alone or a lesser airflow reduction associated with ≥3% desaturation or arousal, using PSGs from APPLES were calculated. A total of 833 adult subjects were included. The DAHI has excellent and strong correlation with the conventionally scored AHI on PSGs, with Pearson coefficients of 0.972 and receiver operating characteristic curves demonstrating strong agreement in all OSA categories: 98.5% in mild OSA (95% confidence interval [CI], 97.6-99.3%), 96.4% in moderate OSA (95% CI, 95.3-97.5%), and 98.5% in severe OSA (95% CI, 97.8-99.2%). An accurate automated AHI can be derived from oximetry and CPC.
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http://dx.doi.org/10.1513/AnnalsATS.202005-510OCDOI Listing
May 2021

Impact of Catheter Ablation on Sleep Quality and Relationship Between Sleep Stability and Recurrence of Paroxysmal Atrial Fibrillation After Successful Ablation: 24-Hour Holter-Based Cardiopulmonary Coupling Analysis.

J Am Heart Assoc 2020 12 26;9(23):e017016. Epub 2020 Nov 26.

Division of Cardiology Hallym University Sacred Heart Hospital Hallym University College of Medicine Anyang Korea.

Background Sleep fragmentation and sleep apnea are common in patients with atrial fibrillation (AF). We investigated the impact of radio-frequency catheter ablation (RFCA) on sleep quality in patients with paroxysmal AF and the effect of a change in sleep quality on recurrence of AF. Methods and Results Of 445 patients who underwent RFCA for paroxysmal AF between October 2007 and January 2017, we analyzed 225 patients who had a 24-hour Holter test within 6 months before RFCA. Sleep quality was assessed by cardiopulmonary coupling analysis using 24-hour Holter data. We compared cardiopulmonary coupling parameters (high-frequency coupling, low-frequency coupling, very-low-frequency coupling) before and after RFCA. Six months after RFCA, the high-frequency coupling (marker of stable sleep) and very-low-frequency coupling (rapid eye movement/wake marker) was significantly increased (29.84%-36.15%; <0.001; and 26.20%-28.76%; =0.002, respectively) while low-frequency coupling (unstable sleep marker) was decreased (41.25%-32.13%; <0.001). We divided patients into 3 tertiles according to sleep quality before RFCA, and the risk of AF recurrence in each group was compared. The second tertile was used as a reference; patients with unstable sleep (Tertile 3) had a significantly lower risk of AF recurrence (hazard ratio [HR], 0.32; 95% CI, 0.12-0.83 for high-frequency coupling; and HR, 0.22; 95% CI, 0.09-0.58 for low-frequency coupling). Conclusions Sleep quality improved after RFCA in patients with paroxysmal AF. The recurrence rate was significantly lower in patients who had unstable sleep before RFCA. These results suggest that RFCA can influence sleep quality, and sleep quality assessment before RFCA may provide a risk marker for recurrence after RFCA in patients with paroxysmal AF.
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http://dx.doi.org/10.1161/JAHA.120.017016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763792PMC
December 2020

Prevalence of Undiagnosed Sleep Apnea in Patients With Atrial Fibrillation and its Impact on Therapy.

JACC Clin Electrophysiol 2020 11 12;6(12):1499-1506. Epub 2020 Aug 12.

Cardiac Electrophysiology Section, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address:

Objectives: This study sought to evaluate the proportion of patients with atrial fibrillation (AF) who also have undiagnosed sleep apnea and examine the impact of its diagnosis on adherence to sleep apnea therapies.

Background: Sleep apnea is a modifiable risk factor for AF. However, the proportion of patients with AF who also have undiagnosed sleep apnea and the impact of its diagnosis on therapy have not been well studied.

Methods: This prospective study included 188 consecutive patients with AF without a prior diagnosis of sleep apnea who were scheduled to undergo AF ablation. Participants underwent home sleep apnea testing, completed a sleep apnea screening questionnaire (STOP-BANG [Snoring; Tiredness, Fatigue, or Sleepiness During the Daytime; Observation of Apnea and/or Choking During Sleep; Hypertension; Body Mass Index >35 kg/m; Age >50 Years; Neck Circumference >40 cm; and Male Sex]) and were followed for ≥2 years to evaluate the impact of diagnosis on therapy.

Results: Home sleep apnea testing was positive in 155 of 188 patients (82.4%); among those 155, 127 (82%) had a predominant obstructive component and 28 (18%) had mixed sleep apnea with a 15.2 ± 7.4% central component. Sleep apnea severity was mild in 43.8%, moderate in 32.9%, and severe in 23.2%. The sensitivity and specificity of a STOP-BANG questionnaire were 81.2% and 42.4%, respectively. In a multivariate analysis, STOP-BANG was not predictive for sleep apnea (odds ratio: 0.54; 95% confidence interval: 0.17 to 1.76; p = 0.31). Therapy with continuous positive airway pressure ventilators was initiated in 73 of 85 patients (85.9%) with moderate or severe sleep apnea, and 68 of the 73 patients (93.1%) remained complaint after a mean follow-up period of 21 ± 6.2 months.

Conclusions: Sleep apnea is exceedingly prevalent in patients with AF who are referred for ablation, with a large proportion being undiagnosed due the limited predictive value of sleep apnea symptoms in this AF population. Screening for sleep apnea resulted in high rate of long-term continuous positive airway pressure adherence.
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http://dx.doi.org/10.1016/j.jacep.2020.05.030DOI Listing
November 2020

A longitudinal observational population-based study of brain volume associated with changes in sleep timing from middle to late-life.

Sleep 2021 04;44(4)

College of Medicine, Korea University, Republic of Korea.

Study Objectives: Sleep behaviors are related to brain structure and function, but the impact of long-term changes in sleep timing on brain health has not been clearly addressed. The purpose of this study was to examine the association of longitudinal changes in sleep timing from middle to late-life with gray matter volume (GMV), an important marker of brain aging.

Methods: We enrolled 1798 adults (aged 49-82 years, men 54.6%) who underwent magnetic resonance imaging (MRI) between 2011 and 2014. Midsleep time (MST) on free days corrected for sleep debt on workdays was adopted as a marker of sleep timing. Data on MST were available at the time of MRI assessment and at examinations that were given 9 years earlier (2003-2004). Longitudinal changes in MST over the 9-year period were derived and categorized into quartiles. Subjects in quartile 1 were defined as "advancers" (MST advanced ≥ 1 h) while those in quartile 4 were defined as "delayers" (MST delayed ≥ 0.2 h). Quartiles 2-3 defined a reference group (MST change was considered modest). The relationship of GMV with MST changes over 9 years was investigated.

Results: Nine-year change in MST were significantly associated with GMV. Compared to the reference group, advancers had smaller GMVs in the frontal and temporal regions. A delay in MST was also associated with smaller cerebellar GMV.

Conclusions: In middle-to-late adulthood, the direction of change in MST is associated with GMV. While advancers and delayers in MST tend to present lower GMV, associations appear to differ across brain regions.
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http://dx.doi.org/10.1093/sleep/zsaa233DOI Listing
April 2021

Algorithm for automatic detection of self-similarity and prediction of residual central respiratory events during continuous positive airway pressure.

Sleep 2021 04;44(4)

Department of Neurology, Massachusetts General Hospital, Boston, MA.

Study Objectives: Sleep-disordered breathing is a significant risk factor for cardiometabolic and neurodegenerative diseases. High loop gain (HLG) is a driving mechanism of central sleep apnea or periodic breathing. This study presents a computational approach that identifies "expressed/manifest" HLG via a cyclical self-similarity feature in effort-based respiration signals.

Methods: Working under the assumption that HLG increases the risk of residual central respiratory events during continuous positive airway pressure (CPAP), the full night similarity, computed during diagnostic non-CPAP polysomnography (PSG), was used to predict residual central events during CPAP (REC), which we defined as central apnea index (CAI) higher than 10. Central apnea labels are obtained both from manual scoring by sleep technologists and from an automated algorithm developed for this study. The Massachusetts General Hospital sleep database was used, including 2466 PSG pairs of diagnostic and CPAP titration PSG recordings.

Results: Diagnostic CAI based on technologist labels predicted REC with an area under the curve (AUC) of 0.82 ± 0.03. Based on automatically generated labels, the combination of full night similarity and automatically generated CAI resulted in an AUC of 0.85 ± 0.02. A subanalysis was performed on a population with technologist-labeled diagnostic CAI higher than 5. Full night similarity predicted REC with an AUC of 0.57 ± 0.07 for manual and 0.65 ± 0.06 for automated labels.

Conclusions: The proposed self-similarity feature, as a surrogate estimate of expressed respiratory HLG and computed from easily accessible effort signals, can detect periodic breathing regardless of admixed obstructive features such as flow limitation and can aid the prediction of REC.
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http://dx.doi.org/10.1093/sleep/zsaa215DOI Listing
April 2021

Association of Sleep Electroencephalography-Based Brain Age Index With Dementia.

JAMA Netw Open 2020 09 1;3(9):e2017357. Epub 2020 Sep 1.

Department of Neurology, Massachusetts General Hospital, Boston.

Importance: Dementia is an increasing cause of disability and loss of independence in the elderly population yet remains largely underdiagnosed. A biomarker for dementia that can identify individuals with or at risk for developing dementia may help close this diagnostic gap.

Objective: To investigate the association between a sleep electroencephalography-based brain age index (BAI), the difference between chronological age and brain age estimated using the sleep electroencephalogram, and dementia.

Design, Setting, And Participants: In this retrospective cross-sectional study of 9834 polysomnograms, BAI was computed among individuals with previously determined dementia, mild cognitive impairment (MCI), or cognitive symptoms but no diagnosis of MCI or dementia, and among healthy individuals without dementia from August 22, 2008, to June 4, 2018. Data were analyzed from November 15, 2018, to June 24, 2020.

Exposure: Dementia, MCI, and dementia-related symptoms, such as cognitive change and memory impairment.

Main Outcomes And Measures: The outcome measures were the trend in BAI when moving from groups ranging from healthy, to symptomatic, to MCI, to dementia and pairwise comparisons of BAI among these groups.

Findings: A total of 5144 sleep studies were included in BAI examinations. Patients in these studies had a median (interquartile range) age of 54 (43-65) years, and 3026 (59%) were men. The patients included 88 with dementia, 44 with MCI, 1075 who were symptomatic, and 2336 without dementia. There was a monotonic increase in mean (SE) BAI from the nondementia group to the dementia group (nondementia: 0.20 [0.42]; symptomatic: 0.58 [0.41]; MCI: 1.65 [1.20]; dementia: 4.18 [1.02]; P < .001).

Conclusions And Relevance: These findings suggest that a sleep-state electroencephalography-based BAI shows promise as a biomarker associated with progressive brain processes that ultimately result in dementia.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.17357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522697PMC
September 2020

Cardiopulmonary coupling-derived sleep quality is associated with improvements in blood pressure in patients with obstructive sleep apnea at high-cardiovascular risk.

J Hypertens 2020 11;38(11):2287-2294

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Objective: Investigate if changes in objective sleep quality index (SQI) assessed through cardiopulmonary-coupling analysis impacts blood pressure (BP) in patients with obstructive sleep apnea at high-cardiovascular risk.

Methods: Secondary analysis of ECG and pulse-oximetry-[oxygen saturation (SpO2)] data from the Heart Biomarker Evaluation in Apnea Treatment study, multicenter, controlled trial in patients with cardiovascular disease and moderate-severe obstructive sleep apnea, randomly assigned to intervention of healthy lifestyle and sleep hygiene education (HLSE; control group), continuous positive airway pressure (CPAP) or nocturnal supplemental oxygen (NSO). Participants with good-quality ECG-signal and SpO2-signal (n = 241) were included.

Results: CPAP-therapy significantly improved BP, with net average improvement in mean arterial blood pressure during sleep (MAP) when compared with nocturnal supplemental oxygen-therapy or healthy lifestyle and sleep education-therapy, -3.92 (P = 0.012) and -3.83 (P = 0.016), respectively. When stratified on the basis of baseline-SQI, CPAP-therapy improves 24-h MAP -3.02 (P = 0.030) and MAP -5.00 (P = 0.001), in patients with compromised baseline-SQI (SQI < 55). Stratifying the cohort based on changes in SQI during the study period (SQI-SQI), controlling for sex, age over 60, apnea-hypopnea index, SpO2 less than 80%, baseline BP and cardiovascular disease, significant differences are observed comparing the groups that Improved-SQI (SQI < 55, SQI ≥ 55) and Declined-SQI (SQI ≥ 55, SQI < 55) in MAP -4.87 (P = 0.046) and mean diastolic blood pressure (MDP) -4.42 (P = 0.026) as well as MAP -6.36 (P = 0.015), mean systolic blood pressure wake (MSP) -7.80 (P = 0.048) and MDP -5.64 (P = 0.009), respectively. Improved SQI reflects the magnitude of positive effect on BP which is reached mostly through initiation of CPAP-therapy.

Conclusion: Cardiopulmonary coupling-derived sleep quality impacted 24-h MAP and MDP, as well as BP during wake, in patients participating in the Heart Biomarker Evaluation in Apnea Treatment-study.
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http://dx.doi.org/10.1097/HJH.0000000000002553DOI Listing
November 2020

Neck Circumference and Cerebral Gray Matter Volume.

Alzheimer Dis Assoc Disord 2020 Oct-Dec;34(4):306-312

Institute of Human Genomic Study, Korea University College of Medicine, Ansan-si.

Background: While obesity is linked with brain atrophy and dementia incidence, associations with regional adiposity are uncertain. Our goal was to determine whether cerebral gray matter volume is related to neck circumference (NC), a measure of regional adiposity having unique relationships with metabolic disorders and cardiovascular disease.

Methods: Magnetic resonance imaging and NC were cross-sectionally assessed from 2011 to 2014 in a population-based sample of 2916 men and women in the Korean Genome and Epidemiology Study.

Results: For men, NC was inversely associated with total and regional gray matter in the frontal, temporal, and occipital lobes after adjusting for age and intracranial brain volume. Associations were especially strong in the presence of diabetes. With further adjustment for indices of body composition and other characteristics, total and frontal gray matter in diabetic men were lowered by 6.1 mL (95% confidence interval: 2.5-9.7, P=0.004) and 2.9 mL (95% confidence interval: 1.0-4.9, P=0.017), respectively, per SD increase in NC (2.3 cm). For men without diabetes, and in all women, associations were less apparent.

Conclusions: In men with diabetes, NC was inversely associated with cerebral gray matter volume. The link between neck anthropometry and brain aging in diabetic men warrants further consideration.
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http://dx.doi.org/10.1097/WAD.0000000000000386DOI Listing
June 2020

Optimal Cancer Care for Aboriginal and Torres Strait Islander People: A Shared Approach to System Level Change.

JCO Glob Oncol 2020 02;6:108-114

Department of Health and Human Services, Melbourne, VIC, Australia.

Purpose: To improve cancer outcomes for Aboriginal and Torres Strait Islander people through the development and national endorsement of the first population-specific optimal care pathway (OCP) to guide the delivery of high-quality, culturally appropriate, and evidence-based cancer care.

Methods: An iterative methodology was undertaken over a 2-year period, and more than 70 organizations and individuals from diverse cultural, geographic, and sectorial backgrounds provided input. Cancer Australia reviewed experiences of care and the evidence base and undertook national public consultation with the indigenous health sector and community, health professionals, and professional colleges. Critical to the OCP development was the leadership of Aboriginal and Torres Strait Islander health experts and consumers.

Results: The OCP received unanimous endorsement by all federal, state, and territory health ministers. Key elements of the OCP include attention to the cultural appropriateness of the health care environment; improvement in cross-cultural communication; relationship building with local community; optimization of health literacy; recognition of men's and women's business; and the need to use culturally appropriate resources. The OCP can be used as a tool for health services and health professionals to identify gaps in current cancer services and to inform quality improvement initiatives across all aspects of the care pathway.

Conclusion: The development of the OCP identified a number of areas that require prioritization. Ensuring culturally safe and accessible health services is essential to support early presentation and diagnosis. Multidisciplinary treatment planning and patient-centered care are required for all Aboriginal and Torres Strait Islander people, irrespective of location. Health planners and governments acknowledge the imperative for change and have expressed strong commitment to work with indigenous Australians to improve the accessibility, cultural appropriateness, and quality of cancer care.
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http://dx.doi.org/10.1200/JGO.19.00076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998013PMC
February 2020

Sleep staging from electrocardiography and respiration with deep learning.

Sleep 2020 07;43(7)

Department of Neurology, Massachusetts General Hospital, Boston, MA.

Study Objectives: Sleep is reflected not only in the electroencephalogram but also in heart rhythms and breathing patterns. We hypothesized that it is possible to accurately stage sleep based on the electrocardiogram (ECG) and respiratory signals.

Methods: Using a dataset including 8682 polysomnograms, we develop deep neural networks to stage sleep from ECG and respiratory signals. Five deep neural networks consisting of convolutional networks and long- and short-term memory networks are trained to stage sleep using heart and breathing, including the timing of R peaks from ECG, abdominal and chest respiratory effort, and the combinations of these signals.

Results: ECG in combination with the abdominal respiratory effort achieved the best performance for staging all five sleep stages with a Cohen's kappa of 0.585 (95% confidence interval ±0.017); and 0.760 (±0.019) for discriminating awake vs. rapid eye movement vs. nonrapid eye movement sleep. Performance is better for younger ages, whereas it is robust for body mass index, apnea severity, and commonly used outpatient medications.

Conclusions: Our results validate that ECG and respiratory effort provide substantial information about sleep stages in a large heterogeneous population. This opens new possibilities in sleep research and applications where electroencephalography is not readily available or may be infeasible.
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http://dx.doi.org/10.1093/sleep/zsz306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355395PMC
July 2020

From protocol to product: ventral midbrain dopaminergic neuron differentiation for the treatment of Parkinson's disease.

Regen Med 2019 11 13;14(11):1057-1069. Epub 2019 Nov 13.

Centre for Biological Engineering, Wolfson School of Mechanical, Electrical & Manufacturing Engineering, Loughborough University, Epinal Way, Loughborough, Leicestershire, LE11 3TU, UK.

Current cell therapy product limitations include the need for in-depth product understanding to ensure product potency, safety and purity. New technologies require development and validation to address issues of production scale-up to meet clinical need; assays are required for process control, validation and release. Prior to clinical realization, an understanding of production processes is required to implement process changes that are essential for process control. Identification of key parameters forms the basis of process tolerances, allowing for validated, adaptive manufacturing processes. This enables greater process control and yield while withstanding regulatory scrutiny. This report summaries key milestones in specifically for ventral midbrain dopaminergic neuroprogenitor differentiation and key translational considerations and recommendations to enable successful, robust and reproducible current cell therapy product-manufacturing.
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http://dx.doi.org/10.2217/rme-2019-0076DOI Listing
November 2019

Alignment with Indices of A Care Pathway Is Associated with Improved Survival: An Observational Population-based Study in Colon Cancer Patients.

EClinicalMedicine 2019 Oct 23;15:42-50. Epub 2019 Aug 23.

University of Melbourne, Victoria, Australia.

Background: Causes of variations in outcomes from cancer care in developed countries are often unclear. Australia has developed health system pathways describing consensus standards of optimal cancer care across the phases of prevention through to follow-up or end-of-life. These Optimal Care Pathways (OCP) were introduced from 2013 to 14. We investigated whether care consistent with the OCP improved outcomes for colon cancer patients.

Methods: Colon patients diagnosed from 2008 to 2014 were identified from the Australian State of Victoria Cancer Registry (VCR) and cases linked with State and Federal health datasets. Surrogate variables describe OCP alignment in our cohort, across three phases of the pathway; prevention, diagnosis and initial treatment and end-of-life. We assessed the impact of alignment on (1) stage of disease at diagnosis and (2) overall survival.

Findings: Alignment with the prevention phase of the OCP occurred for 88% of 13,539 individuals and was associated with lower disease stage at diagnosis (OR = 0.33, 95% confidence interval 0.24 to 0.42), improved crude three-year survival (69.2% versus 62.2%; p < 0.001) and reduced likelihood of emergency surgery (17.7% versus 25.6%, p < 0.001). For patients treated first with surgery (n = 10,807), care aligned with the diagnostic and treatment phase indicators (44% of patients) was associated with a survival benefit (risk-adjusted HR = 1.23, 95% confidence interval 1.13 to 1.35), better perioperative outcomes and higher alignment with follow-up and end-of-life care. The survival benefit persists adjusting for potential confounding factors, including age, sex, disease stage and comorbidity.Interpretation.This population-based study shows that care aligned to a pathway based on best principles of cancer care is associated with improved outcomes for patients with colon cancer.

Funding: None.
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http://dx.doi.org/10.1016/j.eclinm.2019.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833448PMC
October 2019

The pathway to diagnosis and treatment for surgically managed lung cancer patients.

Fam Pract 2020 03;37(2):234-241

Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.

Background: Most lung cancer is diagnosed at an advanced stage, resulting in poor survival. This study examined diagnostic pathways for patients with operable lung cancer to identify factors contributing to early diagnosis.

Methods: Surgically treated lung cancer patients (aged ≥40, within 6 months of diagnosis), approached via the population-based Cancer Registry, with their primary care physicians (PCPs) and specialists completed cross-sectional surveys assessing symptoms, diagnostic route (symptomatic or 'investigation' of other problem), tests, key event dates and treatment. Time intervals to diagnosis and treatment were determined, and quantile regression examined differences between the two diagnostic routes. Cox proportional hazard regression analyses examined associations between survival and diagnostic route adjusting for stage, sex and age.

Results: One hundred and ninety-two patients (36% response rate), 107 PCPs and 55 specialists participated. Fifty-eight per cent of patients had a symptomatic diagnostic route reporting an average of 1.6 symptoms, most commonly cough, fatigue or haemoptysis. Symptomatic patients had longer median primary care interval than 'investigation' patients (12 versus 9 days, P < 0.05) and were more likely to report their PCP first-ordered imaging tests. Secondary care interval was shorter for symptomatic (median = 43 days) than investigation (median = 62 days, P < 0.05) patients. However, 56% of all patients waited longer than national recommendations (6 weeks). While survival estimates were better for investigation than symptomatic patients, these differences were not significant.

Conclusion: Many operable lung cancer patients are diagnosed incidentally, highlighting the difficulty of symptom-based approaches to diagnosing early stage disease. Longer than recommended secondary care interval suggests the need for improvements in care pathways.
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http://dx.doi.org/10.1093/fampra/cmz064DOI Listing
March 2020

The effect of acute exposure to morphine on breathing variability and cardiopulmonary coupling in men with obstructive sleep apnea: A randomized controlled trial.

J Sleep Res 2020 04 21;29(2):e12930. Epub 2019 Oct 21.

Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.

Opioid-related deaths from respiratory depression are increasing but there is only limited information on the effect of morphine on breathing during sleep. This study aimed to detect and quantify opioid-induced cardiorespiratory pattern changes during sleep in obstructive sleep apnea (OSA) patients using novel automated methods and correlate these with conventional polysomnography (PSG) measures. Under a randomized double-blind placebo-controlled crossover design, 60 male OSA patients attended two one-night visits to the sleep laboratory, at least a week apart. Either a 40-mg controlled-release oral morphine dose or placebo was administered. Breathing during sleep was measured by standard in-laboratory PSG. We analysed the inter-breath interval (IBI) from the PSG flow channel to quantify breathing irregularity. Cardiopulmonary coupling (CPC) was analysed using the PSG electrocardiogram (ECG) channel. Following the consumption of morphine, the 60 OSA patients had fewer breaths (p = .0006), a longer inter-breath interval (p < .0001) and more irregular breathing with increased IBI coefficient of variation (CV) (p = .0015) compared to the placebo night. A higher CPC sleep quality index was found with morphine use. The change of key IBI and CPC parameters was significantly correlated with the change of key PSG sleep-disordered breathing parameters. In conclusion, 40 mg controlled-release morphine resulted in a longer breathing cycle and increased breathing irregularity but generally more stable sleep in OSA patients. The significant links between the IBI and CPC techniques and a range of PSG sleep-disordered breathing parameters may suggest a practical value as surrogate overnight cardiorespiratory measurements, because both respiratory flow and ECG can be detected by small portable devices.
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http://dx.doi.org/10.1111/jsr.12930DOI Listing
April 2020

Quantifying statistical uncertainty in metrics of sleep disordered breathing.

Sleep Med 2020 01 13;65:161-169. Epub 2019 Jun 13.

Harvard Medical School, USA; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, USA; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, USA. Electronic address:

Background: The apnea-hypopnea index (AHI) (or one of its derivatives) is the primary clinical metric for characterizing sleep disordered breathing-the value of which with respect to a threshold determines severity of diagnosis and eligibility for treatment reimbursement. The index value, however, is taken as a perfect point estimate, with no measure of statistical uncertainty. Thus, current practice does not robustly account for variability in diagnosis/eligibility due to chance. In this paper, we quantify the statistical uncertainty associated with respiratory event indices for sleep disordered breathing and the effect of uncertainty on treatment eligibility.

Methods: We develop an empirical estimate of uncertainty using a non-parametric bootstrap on the interevent times, as well as a theoretical Poisson estimate reflecting the current formulation of the AHI. We then apply these methods to estimate AHI uncertainty for 2049 subjects (954/1095 M/F, age: mean 69 ± 9.1) from the Multi-Ethnic Study of Atherosclerosis (MESA).

Results And Conclusions: The mean 95% empirical confidence interval width was 11.500 ± 6.208 events per hour and the mean 95% theoretical Poisson confidence interval width was 5.998 ± 2.897 events per hour, suggesting that uncertainty is likely a major confounding factor within the current diagnostic framework. Of the 278 subjects in the symptomatic population (ESS>10), 27% (76/278) had uncertain diagnoses given the 95% empirical confidence interval. Of the 2049 subjects in the full population, 43% (880/2049) had uncertain diagnoses given the 95% empirical confidence interval. The inclusion of subjects with uncertain diagnoses increases the number of eligible patients by 21.3% for the symptomatic population and by 84.8% for the full population. The exclusion of subjects with uncertain diagnoses given the 95% empirical confidence interval decreases the number of eligible patients by 12.4% for the symptomatic population and by 34.8% for full population. Additional analyses suggest that it is practically infeasible to gain diagnostic statistical significance through additional testing for a broad range of borderline cases. Overall, these results suggest that AHI uncertainty is a vital additional piece of information that would greatly benefit clinical practice, and that the inclusion of uncertainty in epidemiological analysis might help improve the ability for researchers to robustly link AHI with co-morbidities and long-term outcomes.
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http://dx.doi.org/10.1016/j.sleep.2019.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938549PMC
January 2020

Thermal damage thresholds for multiple-pulse porcine skin laser exposures at 1070 nm.

J Biomed Opt 2019 09;25(3):1-11

711th Human Performance Wing, Airman Systems Directorate, Bioeffects Division, Optical Radiation Bio, United States.

As solid-state laser technology continues to mature, high-energy lasers operating in the near-infrared (NIR) band have seen increased utilization in manufacturing, medical, and military applications. Formulations of maximum permissible exposure limits establish guidelines for the safe use of these systems for a given set of laser parameters, based on past experimental and analytical studies of exposure thresholds causing injury to the skin and eyes. The purpose of our study is to characterize the skin response to multiple-pulsed laser exposures at the NIR wavelength of 1070 nm, at a constant beam diameter of 1 cm, using anesthetized Yucatan mini-pig subjects. Our study explores three constant total laser-on times of 0.01, 0.1, and 10 s as single- and multiple-pulse sequences. Exposures consisting of 10, 30, and 100 pulses have identical individual pulse durations but different duty cycles in order to include variable degrees of thermal additivity. A plurality of three observers quantifies skin damage with the minimally visible lesion metric, judged at the 1- and 24-h intervals postexposure. Calculation of the median effective dose (ED) provides injury thresholds for all exposure conditions, based on varying laser power across subjects. The results of this study will provide a quantitative basis for the incorporation of multiple-pulsed laser exposure into standards and augment data contained in the existing ED database.
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http://dx.doi.org/10.1117/1.JBO.25.3.035001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011167PMC
September 2019

Concordance between Optimal Care Pathways and colorectal cancer care: Identifying opportunities to improve quality and reduce disparities.

J Eval Clin Pract 2020 Jun 9;26(3):918-926. Epub 2019 Jul 9.

Centre for Behavioural Research in Cancer, Cancer Council Victoria, Melbourne, Australia.

Rationale, Aims, And Objectives: Care pathway policies for cancer aim to reduce variation and improve the quality of patient care, and there is increasing evidence that adherence to such pathways is associated with improved survival and lower health care costs. Australia is implementing Optimal Care Pathways (OCPs) for several cancers, including colorectal cancer, but studies evaluating how well care conforms to OCP recommendations are rare. This study examined concordance between OCP recommendations and colorectal cancer care prior to policy rollout and disparities for vulnerable populations.

Method: Cross-sectional survey (2012-2014) of cancer registry-identified colorectal cancer patients aged ≥40 approached within 6 months of diagnosis (n = 433), their general practitioner (GP, n = 290), and specialist (n = 144) in Victoria, Australia. We measured concordance with 10 OCP recommendations and variation by geography, socio-economic, and health insurance status using age- and sex-adjusted logistic regression models.

Results: Use of recommended GP investigations varied from 66% for colonoscopy to 13% for digital rectal exam. Recommended waiting times to receive a colonoscopy, see a specialist after referral, and begin adjuvant chemotherapy were exceeded for around a third of patients. Twenty-eight percent of specialists reported a pretreatment multidisciplinary meeting. Most patients received surgery in a hospital with an intensive care unit (92%) and chemotherapy for high risk disease (84%). In general, care was similar across sociodemographic groups. However, receipt of GP investigations tended to be higher and waiting times longer for rural, low socio-economic, and non-privately insured patients. For example, receiving a colonoscopy within 4 weeks was significantly less likely for rural (51%) than urban (78%) patients (odds ratio = 0.30; 95% confidence interval, 0.11-0.79).

Conclusion: Prior to implementation, a significant proportion of colorectal cancer patients received care that did not meet OCP recommendations. Low concordance and inequities for rural and disadvantaged populations highlight components of the pathway to target during policy implementation.
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http://dx.doi.org/10.1111/jep.13231DOI Listing
June 2020

Altered structural brain network resulting from white matter injury in obstructive sleep apnea.

Sleep 2019 09;42(9)

Institute of Human Genomic Study, College of Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea.

Study Objectives: To assess, using fractional anisotropy (FA) analysis, alterations of brain network connectivity in adults with obstructive sleep apnea (OSA). Abnormal networks could mediate clinical functional deficits and reflect brain tissue injury.

Methods: Structural brain networks were constructed using diffusion tensor imaging (DTI) from 165 healthy (age 57.99 ± 6.02 years, male 27.9%) and 135 OSA participants (age 59.01 ± 5.91 years, male 28.9%) and global network properties (strength, global efficiency, and local efficiency) and regional efficiency were compared between groups. We examined MRI biomarkers of brain tissue injury using FA analysis and its effect on the network properties.

Results: Differences between groups of interest were noted in global network properties (p-value < 0.05, corrected), and regional efficiency (p-value < 0.05, corrected) in the left middle cingulate and paracingulate gyri, right posterior cingulate gyrus, and amygdala. In FA analysis, OSA participants showed lower FA values in white matter (WM) of the right transverse temporal, anterior cingulate and paracingulate gyri, and left postcentral, middle frontal and medial frontal gyri, and the putamen. After culling fiber tracts through WM which showed significant differences in FA, we observed no group difference in network properties.

Conclusions: Changes in WM integrity and structural connectivity are present in OSA participants. We found that the integrity of WM affected brain network properties. Brain network analysis may improve understanding of neurocognitive deficits in OSA, enable longitudinal tracking, and provides explanations for specific symptoms and recovery kinetics.
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http://dx.doi.org/10.1093/sleep/zsz120DOI Listing
September 2019

The Respiratory Signature: A Novel Concept to Leverage Continuous Positive Airway Pressure Therapy as an Early Warning System for Exacerbations of Common Diseases such as Heart Failure.

J Clin Sleep Med 2019 06 15;15(6):923-927. Epub 2019 Jun 15.

Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Abstract: Each night millions of patients use continuous positive airway pressure (CPAP) to treat obstructive sleep apnea (OSA). To facilitate monitoring of treatment success, modern CPAP machines routinely record and analyze the respiratory signal in near real-time and submit some of these data to the manufacturer's centralized cloud server. Some of the conditions frequently associated with OSA such as heart failure or chronic obstructive pulmonary disease result in characteristic changes of the respiratory signal ("signatures"), especially during exacerbations. Thus, this infrastructure could be leveraged to detect changes in patients' health status facilitating early interventions. To illustrate this concept, we present and discuss the case of a patient with OSA who showed abrupt changes in his breathing pattern (increase in periodic breathing and machine-detected obstructive apneas) from 10 days prior until 8 days after a hospitalization for acute heart failure exacerbation.
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http://dx.doi.org/10.5664/jcsm.7852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557656PMC
June 2019

Using porous iron composite (PIC) material to immobilize rhenium as an analogue for technetium.

Environ Int 2019 07 9;128:379-389. Epub 2019 May 9.

Savannah River Ecology Laboratory, Aiken, SC, USA; The University of Georgia, Athens, GA, USA.

Technetium (Tc), a uranium-235 (U) and plutonium-239 (Pu) fission product, is a primary risk driver in low level radioactive liquid waste at U.S. Department of Energy sites. Previous studies have shown success in using Zero Valent Iron (ZVI) to chemically reduce and immobilize redox sensitive groundwater contaminants. Batch and column experiments were performed to assess the ability of a novel porous iron composite material (PIC) to immobilize Tc(VII) in comparison with two commercial Fe oxide sorbents and reagent grade ZVI in the presence and absence of NO, a competing oxidized species that is often found in high concentrations in liquid nuclear waste. Perrhenate (ReO) was used as a non-radioactive chemical analogue for pertechnetate (TcO) under both oxic and anoxic test conditions. The PIC powder was the most effective at immobilizing Re(VII) under all batch test conditions. The presence of nitrate (NO) slowed the removal of ReO from solution, presumably through chemical reduction and precipitation. Even so, the PIC and ZVI were effective at removing both Re(VII) and NO completely from solution. Nitrate was reduced to NH with very little nitrite (NO) buildup during equilibration. Significant Re immobilization was observed in the column tests containing PIC sorbent, even though inlet solutions were in equilibrium with O. The presence of NO hastened Re breakthrough, while NO reduction to NH was observed. The results suggest that PIC and ZVI would be the most effective at the removal of TcO from contaminated groundwater sites.
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http://dx.doi.org/10.1016/j.envint.2019.05.001DOI Listing
July 2019

Prevalence and Characteristics of Restless Legs Syndrome in Korean Adults: A Study in Two Independent Samples of the General Population.

Neuroepidemiology 2019 14;52(3-4):193-204. Epub 2019 Feb 14.

Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea,

Background: Restless legs syndrome (RLS) is a common sleep disorder, although it has a low prevalence in Asian populations. However, the reported RLS prevalence in -Korean adults is mostly 4.5-12.1%, which is higher than that reported in other Asian populations. This study aimed to diagnose RLS and exclude mimicking conditions in 2 independent samples of Korean adults, and to compare its prevalence to that from previous studies performed in Asian countries.

Methods: Study populations included a (1) nationwide stratified random sample (n = 2,824; age 19-79 years) and (2) community-based cohort (n = 2,685; age 47-79 years). We applied the Cambridge-Hopkins diagnostic questionnaire to diagnose RLS and differentiate it from RLS mimics. Sleep-related symptoms, mood, and medical conditions were compared between the RLS and non-RLS groups. Prior studies of the RLS prevalence in Asia were systematically reviewed and compared to our findings.

Results: The adjusted RLS prevalence was 0.4 and 1.3% in populations 1 and 2, respectively. In both populations, subjects with RLS had more depression. The prevalence of RLS mimics was 5.1 and 2.6%, in populations 1 and 2, respectively. The RLS prevalence in Asia was higher when RLS was defined by the presence of essential clinical features and lower when a differential diagnosis was additionally implemented.

Conclusions: The RLS prevalence in Korean adults considering RLS mimics is comparable to that in adults from other Asian countries (< 2%). The reported RLS prevalence varies depending on the diagnostic method employed.
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http://dx.doi.org/10.1159/000496839DOI Listing
December 2019

Suprathreshold laser injuries in excised porcine skin for millisecond exposures at 1070 nm.

J Biomed Opt 2018 12;23(12):1-11

711th Human Performance Wing, Airman Systems Directorate, Bioeffects Division, Optical Radiation Bio, United States.

Skin injury response to near-infrared (NIR) laser radiation between the minimum visible lesion threshold and ablation onset is not well understood. This study utilizes a 1070-nm diode-pumped Yb-fiber laser to explore the response of excised porcine skin to high-energy exposures in the suprathreshold injury region without inducing ablation. Concurrent high-speed videography is employed to determine a dichotomous response for three progressive damage categories: observable surface distortion, surface bubble formation due to contained intracutaneous water vaporization, and surface bubble rupture during exposure. Median effective dose (ED50) values are calculated in these categories for 3- and 100-ms pulses with beam diameters (1  /  e2) of 3 mm (28, 35, and 49  J  /  cm2) and 7 mm (96, 141, and 212  J  /  cm2), respectively. Double-pulse cases are secondarily investigated. Experimental data are compared with the maximum permissible exposure limits and ablation onset simulated by a one-dimensional multiphysics model. Logistic regression analysis predicted injury events with ∼90  %   of accuracy. The distinction of skin response into progressive damage categories expands the current understanding of high-energy laser safety while underlining the unique biophysical effects during induced water phase change in tissue. These results prove to be useful in the diagnosis and treatment of NIR laser injuries.
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http://dx.doi.org/10.1117/1.JBO.23.12.125001DOI Listing
December 2018

SDNET2018: An annotated image dataset for non-contact concrete crack detection using deep convolutional neural networks.

Data Brief 2018 Dec 6;21:1664-1668. Epub 2018 Nov 6.

Department of Civil and Environmental Engineering, Utah State University, Logan, Utah. USA.

SDNET2018 is an annotated image dataset for training, validation, and benchmarking of artificial intelligence based crack detection algorithms for concrete. SDNET2018 contains over 56,000 images of cracked and non-cracked concrete bridge decks, walls, and pavements. The dataset includes cracks as narrow as 0.06 mm and as wide as 25 mm. The dataset also includes images with a variety of obstructions, including shadows, surface roughness, scaling, edges, holes, and background debris. SDNET2018 will be useful for the continued development of concrete crack detection algorithms based on deep convolutional neural networks (DCNNs), which are a subject of continued research in the field of structural health monitoring. The authors present benchmark results for crack detection using SDNET2018 and a crack detection algorithm based on the AlexNet DCNN architecture. SDNET2018 is freely available at https://doi.org/10.15142/T3TD19.
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http://dx.doi.org/10.1016/j.dib.2018.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247444PMC
December 2018

Science-based assessment of source materials for cell-based medicines: report of a stakeholders workshop.

Regen Med 2018 12 29;13(8):935-944. Epub 2018 Nov 29.

Allan Ritchie Medical Device Consulting, Harrogate, HG1 1BX, UK.

Human pluripotent stem cells (hPSCs) have the potential to transform medicine. However, hurdles remain to ensure safety for such cellular products. Science-based understanding of the requirements for source materials is required as are appropriate materials. Leaders in hPSC biology, clinical translation, biomanufacturing and regulatory issues were brought together to define requirements for source materials for the production of hPSC-derived therapies and to identify other key issues for the safety of cell therapy products. While the focus of this meeting was on hPSC-derived cell therapies, many of the issues are generic to all cell-based medicines. The intent of this report is to summarize the key issues discussed and record the consensus reached on each of these by the expert delegates.
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http://dx.doi.org/10.2217/rme-2018-0120DOI Listing
December 2018

Brain age from the electroencephalogram of sleep.

Neurobiol Aging 2019 02 19;74:112-120. Epub 2018 Oct 19.

Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. Electronic address:

The human electroencephalogram (EEG) of sleep undergoes profound changes with age. These changes can be conceptualized as "brain age (BA)," which can be compared to chronological age to reflect the degree of deviation from normal aging. Here, we develop an interpretable machine learning model to predict BA based on 2 large sleep EEG data sets: the Massachusetts General Hospital (MGH) sleep lab data set (N = 2532; ages 18-80); and the Sleep Heart Health Study (SHHS, N = 1974; ages 40-80). The model obtains a mean absolute deviation of 7.6 years between BA and chronological age (CA) in healthy participants in the MGH data set. As validation, a subset of SHHS containing longitudinal EEGs 5.2 years apart shows an average of 5.4 years increase in BA. Participants with significant neurological or psychiatric disease exhibit a mean excess BA, or "brain age index" (BAI = BA-CA) of 4 years relative to healthy controls. Participants with hypertension and diabetes have a mean excess BA of 3.5 years. The findings raise the prospect of using the sleep EEG as a potential biomarker for healthy brain aging.
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http://dx.doi.org/10.1016/j.neurobiolaging.2018.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478501PMC
February 2019

Obstructive sleep apnea, low transferrin saturation levels, and male-pattern baldness.

Int J Dermatol 2019 Jan 24;58(1):67-74. Epub 2018 Aug 24.

Institute of Human Genomic Study, Korea University Ansan Hospital, Ansan, Korea.

Background: There are limited data on the association between obstructive sleep apnea (OSA), which is characterized by intermittent hypoxia, and male-pattern baldness (MPB). Low blood iron levels are reportedly associated with hypoxia and hair loss. This study explored a possible link among OSA, iron status, and MPB.

Methods: Polysomnography (PSG) and hair assessments were conducted in a cross-sectional study including 932 men aged 46-76 years. OSA was defined as an apnea-hypopnea index ≥5 by PSG evaluation and MPB as scales from IV to VII according to the Norwood-Hamilton scale classification. Serum transferrin saturation (TSA) levels were assessed.

Results: A total of 224 men (24%) were identified as MPB cases and 495 men (53%) as having OSA. After considering potential risk factors, OSA and other sleep-related variables were not associated with MPB. In joint analysis of OSA and family history of hair loss, men with these two factors showed a sevenfold higher multivariate odds ratio (95% confidence interval: 3.70, 12.56) for MPB than those without both of them (P < 0.05 for the interaction between OSA and family history of hair loss). TSA levels were significantly associated with MPB and OSA. OSA cases without MPB as well as MPB cases showed lower TSA levels than those with neither OSA nor MPB (P < 0.05).

Conclusions: These findings suggest that OSA may be a risk factor for MPB in men who have a family history of hair loss and that low serum TSA levels associated with hypoxia may be involved in a pathway linking OSA and MPB.
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http://dx.doi.org/10.1111/ijd.14193DOI Listing
January 2019
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